Plumbagin: A Promising In Vivo Antiparasitic Candidate against Schistosoma mansoni and In Silico Pharmacokinetic Properties (ADMET).

Schistosomiasis, a potentially fatal chronic disease whose etiological agents are blood trematode worms of the genus Schistosoma spp., is one of the most prevalent and debilitating neglected diseases. The treatment of schistosomiasis depends exclusively on praziquantel (PZQ), a drug that has been used since the 1970s and that already has reports of reduced therapeutic efficacy, related with the development of Schistosoma-resistant or -tolerant strains. Therefore, the search for new therapeutic alternatives is an urgent need. Plumbagin (PLUM), a naphthoquinone isolated from the roots of plants of the genus Plumbago, has aroused interest in research due to its antiparasitic properties against protozoa and helminths. Here, we evaluated the in vivo schistosomicidal potential of PLUM against Schistosoma mansoni and the in silico pharmacokinetic parameters. ADMET parameters and oral bioavailability were evaluated using the PkCSM and SwissADME platforms, respectively. The study was carried out with five groups of infected mice and divided as follows: an untreated control group, a control group treated with PZQ, and three groups treated orally with 8, 16, or 32 mg/kg of PLUM. After treatment, the Kato-Katz technique was performed to evaluate a quantity of eggs in the feces (EPG). The animals were euthanized for worm recovery, intestine samples were collected to evaluate the oviposition pattern, the load of eggs was determined on the hepatic and intestinal tissues and for the histopathological and histomorphometric evaluation of tissue and hepatic granulomas. PLUM reduced EPG by 65.27, 70.52, and 82.49%, reduced the total worm load by 46.7, 55.25, and 72.4%, and the female worm load by 44.01, 52.76, and 71.16%, for doses of 8, 16, and 32 mg/kg, respectively. PLUM also significantly reduced the number of immature eggs and increased the number of dead eggs in the oogram. A reduction of 36.11, 46.46, and 64.14% in eggs in the hepatic tissue, and 57.22, 65.18, and 80.5% in the intestinal tissue were also observed at doses of 8, 16, and 32 mg/kg, respectively. At all doses, PLUM demonstrated an effect on the histopathological and histomorphometric parameters of the hepatic granuloma, with a reduction of 41.11, 48.47, and 70.55% in the numerical density of the granulomas and 49.56, 57.63, and 71.21% in the volume, respectively. PLUM presented itself as a promising in vivo antiparasitic candidate against S. mansoni, acting not only on parasitological parameters but also on hepatic granuloma. Furthermore, in silico, PLUM showed good predictive pharmacokinetic profiles by ADMET.

Low Pre-Season Hamstring-to-Quadriceps Strength Ratio Identified in Players Who Further Sustained In-Season Hamstring Strain Injuries: A Retrospective Study from a Brazilian Serie A Team.

A common pre-season injury prevention assessment conducted by professional football clubs is the hamstring-to-quadriceps (H:Q) strength ratio calculated by peak torque (PT). However, it is debatable whether players that present low pre-season H:Q ratios are more susceptible to further sustaining in-season hamstring strain injuries (HSI). Based upon retrospective data from a Brazilian Serie A football squad, a particular season came to our attention as ten out of seventeen (~59%) professional male football players sustained HSI. Therefore, we examined the pre-season H:Q ratios of these players. H:Q conventional (CR) and functional (FR) ratios, and the respective knee extensor/flexor PT from the limbs of players further sustaining in-season HSI (injured players, IP) were compared to the proportional number of dominant/non-dominant limbs from uninjured players (UP) in the squad. FR and CR were ~18-22% lower (p < 0.01), whereas quadriceps concentric PT was ~25% greater for IP than UP (p = 0.002). Low scores of FR and CR were correlated (p < 0.01) with high levels of quadriceps concentric PT (r = -0.66 to -0.77). In conclusion, players who sustained in-season HSI had lower pre-season FR and CR compared to UP, which appears to be associated with higher levels of quadriceps concentric torque than hamstring concentric or eccentric torque.

Sublethal concentrations of usnic acid potassium salt impairs physiological parameters of Biomphalaria glabrata (Say, 1818) (Pulmonata: Planorbidae) infected and not infected with Schistosoma mansoni.

Schistosomiasis is a public health problem in many developing countries. The mollusc Biomphalaria glabrata is the most important vector of Schistosoma mansoni in South America. The population control of this vector to prevent the spread of schistosomiasis is currently done with the application of highly toxic molluscicide to the environment. The screening of substances in sublethal concentrations that have deleterious effects on physiological parameters is very relevant for the control of schistosomiasis, since the effectiveness of disease prevention increases if it acts on population control of the vector and on reproduction and elimination in S. mansoni cercariae. The objective of this study was to evaluate the reproductive parameters (fecundity and fertility), intra-mollusk effect (sporocysts I (72 h) and II (14 days after)) on the development of cercariae of S. mansoni and the immune cell profile of B. glabrata exposed to sublethal concentrations (LC25 - 0.5 µg/mL and LC50 - 0.92 µg/mL) of the usnic acid potassium salt (potassium usnate). LC 25 and LC 50 significantly reduced (p < 0.05) the fecundity of B. glabrata when treated infected and/or not exposed to infection, while unviable embryos were not observed in sporocyst stage I, being only significant (p < 0.05) for mollusks infected and treated with LC50 on sporocyst II. LC25 and LC50 of the potassium usnate caused significant reductions (p < 0.05) in the production and cercarial shedding when evaluated on sporocysts I and II. In addition, the mortality of infected and treated B. glabrata in the sporocyst II phase was quite marked after the 9th week of infection. Regarding the immunological cell profile of uninfected B. glabrata, both concentrations led to immunomodulatory responses, with significant morphological changes predominant of hemocytes that entered programmed cell death (apoptosis). It was concluded that the application of LC25 and LC50 from the potassium usnate could be useful in the population control of B. glabrata, since it interferes both in their biology and physiology and in the reproduction of the infectious agent of schistosomiasis mansoni.

In vitro activity of usnic acid potassium salt against different developmental stages of Schistosoma mansoni: An ultrastructural study.

Currently, the control of schistosomiasis is based on a single drug, praziquantel, which is effective against all species of Schistosoma but only in the adult stage, presenting a schistosomicidal deficit at the other developmental stages of the parasites. Recently our research group has demonstrated that the potassium salt of usnic acid (PS-UA) presented schistosomicidal property against couples of adult worms of S. mansoni. Thus, the present study seeks to report for the first time the in vitro activity of PS-UA against different developmental stages of S. mansoni (schistosomules and young worms). As schistosomicide parameters, we evaluated motility, mortality, cell viability of the worms and tegument changes by scanning electron microscopy (SEM). After 3 h exposure, PS-UA was lethal to schistosomules at concentrations of 100 and 50 µM, whereas for concentrations 25 and 12.5 µM, 38 and 18% of mortality and 62 and 24% changes in motility, respectively, were reached. Yet for schistosomules, concentration of 25 µM caused 90 and 100% of death after 6 and 12 h, respectively. In the concentration of 12.5 µM at intervals of 12 and 24 h mortality was 68 and 100%, respectively. For young worms, after 3 h of exposure at concentrations of 200 and 100 µM caused 57 and 27% mortality, respectively. After 12 and 24 h, these concentrations caused mortality of 90 and 100% and 47 and 60% respectively. After 24 h, concentrations of 50 and 25 µM caused 80 and 30% change in motility, respectively. However, at the 12.5 µM concentration no change was observed. In addition, PS-UA reduced the cellular viability of young worms by 50.98% and 85.87% at concentrations of 100 and 200 µM, respectively. In both stages of worms and at different exposure intervals, PS-UA caused alterations such as: dorsoventral contraction, peeling, swelling, blisters, erosion, exposure of subtegumental tissue and disintegration of tegument. According to the results, changes in motility and mortality caused by PS-UA against schistosomules and young worms were concentration and time-dependents, also PS-UA even at low concentration, was able to cause profound ultrastructural changes in the integument of the worms. PS-UA is a promising candidate as prophylactic agent in the control of schistosomiasis mansoni.

Evaluation of different samplers and storage temperature effect on the methane carbon stable isotope analysis.

The present work evaluates the efficiency of some low-cost sampler container for a reliable carbon stable isotope analysis of methane. The procedure efficiency was evaluated for five containers, through 91 days, under two storage temperatures (4 °C and 25 °C) and the results are compared against a reference sampler by using univariate and multivariate statistical methods. Based on the univariate (ANOVA and comparison statistical methods) and multivariate (PCA and HCA) statistical methods, it was identified that (i) the isotopic value changes with time and, in this way, must be taken in account when choosing the appropriate sampler and (ii) the lower temperature reduces the isotopic fractionation process and is preferable for the gas sample storage. Among the storage systems, two options were found to be statistically equivalent to the reference container (IsoJar) for a time horizon of 91 days. We found that the exetainer (4 °C and 25 °C) storage systems are statistically equivalent to the reference container IsoJar and, in this way, it could be an alternative for the methane isotopic studies.

Flame retardant and hydrophobic coatings on cotton fabrics via sol-gel and self-assembly techniques.

Nanocoatings consisting of ammonium polyphosphate (APP), sodium montmorillonite (MMT), and vinyltrimethoxysilane (VTMS) were prepared via self-assembly and in situ sol-gel techniques and applied onto cotton fabrics to achieve both flame retardancy and hydrophobicity. The impacts of APP concentration on the hydrophobicity and fire resistance of the coated fabrics were investigated. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) characterization results verified the hydrolysis-condensation reaction of VTMS and the formation of Si-O-Si network structure. X-ray diffraction (XRD) proved the formation of a layered structure based on MMT nanosheets in the coatings. Both vertical flame test (VFT), limiting oxygen index (LOI), thermogravimetric analysis (TGA) and microscale combustion calorimeter (MCC) characterization were conducted to evaluate the flame retardancy, thermostability and heat release behavior of the coated cotton fabrics, respectively. The results suggested that a higher concentration of APP is beneficial for both hydrophobicity and flame retardancy of the coated substrates. Overall, our research provides a facile and very effective approach to prepare flame retardant and hydrophobic multifunctional coating for cotton fabric and other substrates.